Synapse structure and function

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Synapse structure and function

Synapse structure and function

CHEMICAL SYNAPSES

Most signaling between nerve cells occurs via chemical synapses.
These are formed by the close association of an axon terminal of the presynaptic cell with some part of the postsynaptic cell.
The gap between the cells, the synaptic cleft, is typically 20 nm across though in some synapses can be much wider.
Synapses are classified by where on the receiving cell they are located. Most are axodendritic synapses made on dendrites; on spiny dendrites, synapses are formed on spines.
Particularly powerful are axosomatic synapses made on the cell body (named for an alternative term for the nerve cell body, the soma).
Synapses between axon terminals and axons of postsynaptic neurons are axoaxonal synapses.

MORPHOLOGY OF CHEMICAL SYNAPSES

Electron microscopy has revealed numerous morphologically distinct types of synapses, but all share common features.
Spherical, clear, small synaptic vesicles (SSVs), 50 nm across, store neurotransmitters and are scattered throughout the terminal in association with microtubules that transport them to the presynaptic membrane.
The presynaptic membrane is thickened and may have dense projections which are involved in the docking of synaptic vesicles at the active zone, the region from which transmitter release occurs.
The dendrite cell membrane at the synapse is thickened as the postsynaptic density, formed by the proteins that constitute the postsynaptic machinery.
Cortical axodendritic synapses are asymmetrical in that they have an extremely well-developed postsynaptic density, they are usually excitatory.
Axosomatic synapses are symmetrical in having pre-and postsynaptic densities of comparable thickness, they are usually inhibitory. The cerebral cortex may have as many as 1013 synapses.

Some synapses lack obviously specialized contact zones on both pre-and postsynaptic sides and have extremely wide (100–500 nm) synaptic clefts.
These often secrete a catecholamine and have large dense-core vesicles (LDCVs) 40–120 nm across. LDCVs are also found in peptide-secreting neurons.
Many synapses contain both SSVs and LDCVs. This structural evidence supports physiological studies showing that many neurons secrete more than one transmitter.

CHEMICAL TRANSMISSION

Most synapses are chemical. At a typical CNS synapse, the arrival of an action potential at the axon terminal may, or may not, trigger the release of neurotransmitters from a single presynaptic vesicle.
Transmitter release requires a rise in intracellular Ca2+ brought about by calcium entry into the axon terminal via voltage-dependent calcium channels.
The transmitter diffuses across the synaptic cleft in about 5 μs. At the postsynaptic membrane, it binds to specific receptors, causing a change in the receptor conformation.
What happens next depends on the receptor, but the overall result is to change the postsynaptic membrane permeability to specific ions.

Synapse structure and function — **Figure 2. A type I synapse containing both small clear vesicles and large dense-core vesicles.**

Neurotransmitter receptors come in two superfamilies.
The ligand-gated ion channels (LGICs), also referred to as ionotropic receptors, have ion-selective channels as part of the receptor.
The binding of the transmitter to the receptor opens the channel, directly increasing its permeability.
The second superfamily is the G-protein-coupled receptors (GPCRs). These are the largest group of metabotropic receptors, so-called because they can modulate metabolic activities.
The binding of the transmitter to these receptors activates their associated G proteins that are capable of diverse and remote effects on membrane permeability, excitability, and metabolism.
G proteins can influence permeability either by binding ion channels directly or by modifying the activity of second messenger system enzymes which phosphorylate ion channels, thereby altering their permeability.
The changes in membrane properties brought about by a transmitter produce postsynaptic potentials, small shifts in the membrane potential that can have essentially one of two effects.
It may increase the probability that the postsynaptic neuron fires action potentials, in which case the response is excitatory.
If the effect is to decrease the probability that the postsynaptic cell might fire, the response is inhibitory.
It is commonly the case that a transmitter is excitatory at one of its receptors, but inhibitory at another, so it is a synapse that is excitatory or inhibitory rather than the transmitter per se.
Numerous molecules have been identified as neurotransmitters.
The classical transmitters are small molecules, amino acids, or amines. Quantitatively by far, the most important is glutamate, which is almost invariably excitatory, and g-aminobutyrate (GABA) which is usually inhibitory. This group also includes acetylcholine, the catecholamines such as dopamine and noradrenaline (norepinephrine), and the indoleamine, serotonin. A second, larger, group is an eclectic mix of peptides which includes the opioids (such as endorphins) and tachykinins (e.g., substance P).
Fast transmission occurs whenever a neurotransmitter acts via LGICs, whereas slow transmission occurs when transmitters act at GPCRs.
Glutamate, GABA, and acetylcholine (ACh) are together responsible for most fast transmission.
However, each of these molecules also mediates slow transmission by activating their corresponding GPCR. Indeed, a transmitter can mediate both fast and slow transmission at the same synapse by activating multiple receptor populations.
For example, ACh released from preganglionic cells acts on both nicotinic and muscarinic receptors on postganglionic cells in autonomic ganglia, mediating fast and slow effects of ACh respectively.
Catecholamine and peptide transmission are invariably slow.

It is extremely common for a given synapse to release more than one transmitter.
This transmission usually involves the release of a classical transmitter, coupled with the co-release of one or more peptides at higher firing frequencies.
Transmitters are rapidly cleared from the synaptic cleft after release by passive diffusion away from the cleft, reuptake into surrounding neurons or glia, or enzyme degradation.

ELECTRICAL TRANSMISSION

Electrical transmission is mediated by electrical synapses, which are gap junctions between adjacent neurons. Gap junctions are arrays of paired hexameric ion channels called connexons.
The channel pores are 2–3 nm in diameter, allowing ions and small molecules to permeate between neighboring neurons.
By electrically coupling neurons, gap junctions allow any potentials, for example, action potentials, to spread between cells.
Key features of electrical transmission are that it is extremely rapid, signals are transmitted with no distortion, and it works in both directions.
Gap junctions between cells can close. Each connexon is made up of six subunits called connexins, and in response to a rise in intracellular Ca2+ concentration, the connexins rotate to close the central pore.

4 2 — **Figure 3.** (a) Gap junction. (b) Change in the configuration of the connexons to close a gap junction.

References